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1.
ACS Appl Bio Mater ; 7(5): 3215-3226, 2024 May 20.
Article En | MEDLINE | ID: mdl-38695746

This study presents a tetra-substituted phthalonitrile derivative, namely, diethyl 2-(3,4-dicyano-2,5-bis(hexyloxy)-6-(4-(trifluoromethoxy)phenoxy)phenyl)malonate (a), cyclotetramerizing in the presence of some metal salts. The resultant hexadeca-substituted metal phthalocyanines [M= Co, Zn, InCl)] (b-d) were used for the modification of reduced graphene oxide for the first time. The effect of the phthalonitrile/metal phthalocyanines on biological features of reduced graphene oxide (rGO) was extensively examined by the investigation of antioxidant, antimicrobial, DNA cleavage, cell viability, and antibiofilm activities of nanobioagents (1-4). The results were compared with those of unmodified rGO (nanobioagent 5), as well. Modification of reduced graphene oxide with the synthesized compounds improved its antioxidant activity. The antioxidant activities of all the tested nanobioagents also enhanced as the concentration increased. The antibacterial activities of all the nanobioagents improved by applying the photodynamic therapeutic (PDT) method. All the phthalonitrile/phthalocyanine-based nanobioagents (especially phthalocyanine-based nanocomposites) exhibited DNA cleavage activities, and complete DNA fragmentation was observed for nanobioagents (1-4) at 200 mg/L. They can be used as potent antimicrobial and antimicrobial photodynamic therapy agents as well as Escherichia coli microbial cell inhibitors. As a result, the prepared nanocomposites can be considered promising candidates for biomedicine.


Anti-Bacterial Agents , Biocompatible Materials , Graphite , Indoles , Isoindoles , Materials Testing , Particle Size , Graphite/chemistry , Graphite/pharmacology , Indoles/chemistry , Indoles/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/chemical synthesis , Microbial Sensitivity Tests , Cell Survival/drug effects , Escherichia coli/drug effects , Molecular Structure , Biofilms/drug effects , Humans , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/chemical synthesis , Oxides/chemistry , Oxides/pharmacology
2.
J Dent ; 145: 105033, 2024 Jun.
Article En | MEDLINE | ID: mdl-38697505

OBJECTIVES: This study aimed to enhance gingival fibroblast function and to achieve antibacterial activity around the implant abutment by using a zinc (Zn)-containing bioactive glass (BG) coating. METHODS: 45S5 BG containing 0, 5, and 10 wt.% Zn were coated on zirconia disks. The release of silica and Zn ions in physiological saline and their antibacterial effects were measured. The effects of BG coatings on human gingival fibroblasts (hGFs) were assessed using cytotoxicity assays and by analyzing the gene expression of various genes related to antioxidant enzymes, wound healing, and fibrosis. RESULTS: BG coatings are capable of continuous degradation and simultaneous ion release. The antibacterial effect of BG coatings increased with the addition of Zn, while the cytotoxicity remained unchanged compared to the group without coatings. BG coating enhances the expression of angiogenesis genes, while the Zn-containing BG enhances the expression of antioxidant genes at an early time point. BG coating enhances the expression of collagen genes at later time points. CONCLUSIONS: The antibacterial effect of BG improved with the increase in Zn concentration, without inducing cytotoxicity. BG coating enhances the expression of angiogenesis genes, and Zn-containing BG enhances the expression of antioxidant genes at an early time point. BG coating enhances the expression of collagen genes at later time points. CLINICAL SIGNIFICANCE: Adding 10 wt% Zn to BG could enhance the environment around implant abutments by providing antibacterial, antioxidant, and anti-fibrotic effects, having potential for clinical use.


Anti-Bacterial Agents , Ceramics , Dental Abutments , Fibroblasts , Gingiva , Glass , Surface Properties , Zinc , Zirconium , Zirconium/pharmacology , Zirconium/chemistry , Humans , Zinc/pharmacology , Fibroblasts/drug effects , Anti-Bacterial Agents/pharmacology , Gingiva/cytology , Gingiva/drug effects , Glass/chemistry , Ceramics/pharmacology , Ceramics/chemistry , Coated Materials, Biocompatible/pharmacology , Coated Materials, Biocompatible/chemistry , Antioxidants/pharmacology , Materials Testing , Collagen , Wound Healing/drug effects , Dental Materials/pharmacology , Dental Materials/chemistry , Cells, Cultured
3.
ACS Appl Bio Mater ; 7(5): 3330-3336, 2024 May 20.
Article En | MEDLINE | ID: mdl-38701398

The threat of bacterial infections, especially drug-resistant strains, to human health necessitates the development of high-efficient, broad-spectrum and nonantibiotic nanodisinfectant. However, the effect of interfacial charge on the antibacterial properties of nanodisinfectant remains a mystery, which greatly limits the development of highly antibacterial active nanodisinfectant. Herein, we developed three types of ultrasmall (d < 3 nm) gold-nanoparticles (AuNPs) modified with 5-carboxylic(C)/methoxy(M)amino(A)/-2-mercaptobenzimidazole (C/M/A MB) to investigate their interfacial charge on antibacterial performance. Our results showed that both the electropositive AMB-AuNPs and electronegative CMB-AuNPs exhibited no antibacterial activity against both Gram-positive (G+) and Gram-negative (G-) bacteria. However, the electroneutral MMB-AuNPs exhibited unique antibacterial performance against both G+ and G- bacteria, even against methicillin-resistant Staphylococcus aureus (MRSA). Mechanistic investigation revealed a multipathway synergistic bacteriostatic mechanism involving MMB-AuNPs inducing damage to bacterial cell membranes, disruption of membrane potential and downregulation of ATP levels, ultimately leading to bacterial demise. Furthermore, two additional electroneutral AuNPs modified with 5-methyl-2-mercaptobenzimidazole (mMB-AuNPs) and 5-ethoxy-2-mercaptobenzimidazole (EMB-AuNPs) also demonstrated commendable antibacterial efficacy against E. coli, S. aureus, and MRSA; however, their performance was comparatively inferior to that of MMB-AuNPs. This work provides valuable insights for the development of high-performance antibacterial nanomaterials.


Anti-Bacterial Agents , Benzimidazoles , Gold , Metal Nanoparticles , Microbial Sensitivity Tests , Particle Size , Gold/chemistry , Gold/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Metal Nanoparticles/chemistry , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Materials Testing , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Drug Resistance, Bacterial/drug effects
4.
BMC Oral Health ; 24(1): 525, 2024 May 03.
Article En | MEDLINE | ID: mdl-38702623

OBJECTIVE: To evaluate the antibacterial effectiveness of a combination of ε-poly-L-lysine (ε-PL), funme peptide (FP) as well as domiphen against oral pathogens, and assess the efficacy of a BOP® mouthwash supplemented with this combination in reducing halitosis and supragingival plaque in a clinical trial. MATERIALS AND METHODS: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the compound against Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were determined by the gradient dilution method. Subsequently, the CCK-8 assay was used to detect the toxicity of mouthwash on human gingival fibroblastst, and the effectiveness in reducing halitosis and supragingival plaque of the mouthwash supplemented with the combination was analyzed by a randomized, double-blind, parallel-controlled clinical trial. RESULTS: The combination exhibited significant inhibitory effects on tested oral pathogens with the MIC < 1.56% (v/v) and the MBC < 3.13% (v/v), and the mouthwash containing this combination did not inhibit the viability of human gingival fibroblasts at the test concentrations. The clinical trial showed that the test group displayed notably lower volatile sulfur compounds (VSCs) at 0, 10, 24 h, and 7 d post-mouthwash (P < 0.05), compared with the baseline. After 7 days, the VSC levels of the and control groups were reduced by 50.27% and 32.12%, respectively, and notably cutting severe halitosis by 57.03% in the test group. Additionally, the Plaque Index (PLI) of the test and control group decreased by 54.55% and 8.38%, respectively, and there was a significant difference in PLI between the two groups after 7 days (P < 0.01). CONCLUSIONS: The combination of ε-PL, FP and domiphen demonstrated potent inhibitory and bactericidal effects against the tested oral pathogens, and the newly formulated mouthwash added with the combination exhibited anti-dental plaque and anti-halitosis properties in a clinical trial and was safe. TRIAL REGISTRATION: The randomized controlled clinical trial was registered on Chinese Clinical Trial Registry (No. ChiCTR2300073816, Date: 21/07/2023).


Dental Plaque , Halitosis , Mouthwashes , Polylysine , Humans , Halitosis/prevention & control , Halitosis/drug therapy , Halitosis/microbiology , Mouthwashes/therapeutic use , Dental Plaque/microbiology , Dental Plaque/prevention & control , Double-Blind Method , Male , Female , Polylysine/therapeutic use , Adult , Microbial Sensitivity Tests , Young Adult , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Porphyromonas gingivalis/drug effects , Fusobacterium nucleatum/drug effects , Fibroblasts/drug effects , Peptides/therapeutic use , Peptides/pharmacology , Aggregatibacter actinomycetemcomitans/drug effects , Streptococcus mutans/drug effects
5.
Aquat Toxicol ; 271: 106925, 2024 Jun.
Article En | MEDLINE | ID: mdl-38718521

Excessive antibiotic use has led to the spread of antibiotic resistance genes (ARGs), impacting gut microbiota and host health. However, the effects of antibiotics on amphibian populations remain unclear. We investigated the impact of oxytetracycline (OTC) and ciprofloxacin (CIP) on Chinese giant salamanders (Andrias davidianus), focusing on gut microbiota, ARGs, and gene expression by performing metagenome and transcriptome sequencing. A. davidianus were given OTC (20 or 40 mg/kg) or CIP (50 or 100 mg/kg) orally for 7 days. The results revealed that oral administration of OTC and CIP led to distinct changes in microbial composition and functional potential, with CIP treatment having a greater impact than OTC. Antibiotic treatment also influenced the abundance of ARGs, with an increase in fluoroquinolone and multi-drug resistance genes observed post-treatment. The construction of metagenome-assembled genomes (MAGs) accurately validated that CIP intervention enriched fish-associated potential pathogens Aeromonas hydrophila carrying an increased number of ARGs. Additionally, mobile genetic elements (MGEs), such as phages and plasmids, were implicated in the dissemination of ARGs. Transcriptomic analysis of the gut revealed significant alterations in gene expression, particularly in immune-related pathways, with differential effects observed between OTC and CIP treatments. Integration of metagenomic and transcriptomic data highlighted potential correlations between gut gene expression and microbial composition, suggesting complex interactions between the host gut and its gut microbiota in response to antibiotic exposure. These findings underscore the importance of understanding the impact of antibiotic intervention on the gut microbiome and host health in amphibians, particularly in the context of antibiotic resistance and immune function.


Anti-Bacterial Agents , Ciprofloxacin , Gastrointestinal Microbiome , Oxytetracycline , Urodela , Animals , Oxytetracycline/toxicity , Gastrointestinal Microbiome/drug effects , Ciprofloxacin/pharmacology , Ciprofloxacin/toxicity , Urodela/genetics , Urodela/microbiology , Anti-Bacterial Agents/toxicity , Anti-Bacterial Agents/pharmacology , Transcriptome/drug effects , Metagenome , Metagenomics , Gene Expression Profiling , Water Pollutants, Chemical/toxicity , Aeromonas hydrophila/drug effects , Gene Expression Regulation/drug effects
7.
Fish Shellfish Immunol ; 149: 109615, 2024 Jun.
Article En | MEDLINE | ID: mdl-38719095

Curcumin (Cur) exhibits diverse natural pharmacological activities, despite its limited water solubility (hydrophobicity) and low bioavailability. In this investigation, a valine-curcumin conjugate (Val-Cur) was synthesized through amino acid side chain modification, and its solubility increased to 1.78 mg/mL. In vitro experimental findings demonstrated that the antibacterial activity of Val-Cur against Escherichia coli, Staphylococcus aureus, Aeromonas hydrophila, and Vibrio parahaemolyticus was significantly superior to that of Cur. The inhibition rate of Val-Cur against HepG2 (human hepatocellular carcinoma) cells was higher than that of Cur at low concentrations (below 25 µmol/L), although the IC50 value of Val-Cur did not differ significantly from that of Cur. In vivo biological effects of Val-Cur were assessed by adding it into the feed (150 mg/kg) of American eels (Anguilla rostrata). Val-Cur significantly improved the growth performance (↑weight gain rate, ↑specific growth rate, and ↓feed conversion rate) and activities of intestinal digestive enzymes (amylase and lipase) and antioxidant enzymes (superoxide dismutase) in American eels. Additionally, Val-Cur significantly improved serum biochemical indices (↑high-density lipoprotein cholesterol, ↓low-density lipoprotein cholesterol, ↓aspartate and alanine aminotransferases). Furthermore, Val-Cur increased intestinal microbial diversity, reduced the abundance of potentially pathogenic bacteria (Spiroplasma, Clostridium, and Pseudomonas), and elevated the abundance of beneficial digestion-promoting bacteria (Romboutsia, Phyllobacterium, Romboutsia sedimentorum, and Clostridium butyricum) conducive to glucose metabolism (P < 0.05). To the best of our knowledge, this study is the first to explore water-soluble curcumin in aquaculture, and the findings will lay the groundwork for the potential application of water-soluble curcumin in the field of aquaculture.


Anguilla , Anti-Bacterial Agents , Antineoplastic Agents , Curcumin , Animals , Curcumin/pharmacology , Curcumin/chemistry , Curcumin/administration & dosage , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Valine/pharmacology , Valine/chemistry , Animal Feed/analysis , Diet/veterinary , Humans , Dietary Supplements/analysis , Vibrio parahaemolyticus/drug effects , Vibrio parahaemolyticus/physiology , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Hep G2 Cells , Aeromonas hydrophila/physiology , Aeromonas hydrophila/drug effects
8.
ACS Appl Bio Mater ; 7(5): 3164-3178, 2024 May 20.
Article En | MEDLINE | ID: mdl-38722774

Microbial biofilm accumulation poses a serious threat to the environment, presents significant challenges to different industries, and exhibits a large impact on public health. Since there has not been a conclusive answer found despite various efforts, the potential green and economical methods are being focused on, particularly the innovative approaches that employ biochemical agents. In the present study, we propose a bio-nanotechnological method using magnetic cross-linked polyphenol oxidase aggregates (PPO m-CLEA) for inhibition of microbial biofilm including multidrug resistant bacteria. Free PPO solution showed only 55-60% biofilm inhibition, whereas m-CLEA showed 70-75% inhibition, as confirmed through microscopic techniques. The carbohydrate and protein contents in biofilm extracellular polymeric substances (EPSs) were reduced significantly. The m-CLEA demonstrated reusability up to 5 cycles with consistent efficiency in biofilm inhibition. Computational work was also done where molecular docking of PPO with microbial proteins associated with biofilm formation was conducted, resulting in favorable binding scores and inter-residual interactions. Overall, both in vitro and in silico results suggest that PPO interferes with microbial cell attachment and EPS formation, thereby preventing biofilm colonization.


Anti-Bacterial Agents , Biofilms , Catechol Oxidase , Particle Size , Biofilms/drug effects , Catechol Oxidase/metabolism , Catechol Oxidase/chemistry , Catechol Oxidase/antagonists & inhibitors , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Materials Testing , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Microbial Sensitivity Tests , Cross-Linking Reagents/chemistry , Cross-Linking Reagents/pharmacology , Molecular Docking Simulation , Escherichia coli/drug effects
9.
ACS Appl Bio Mater ; 7(5): 3283-3294, 2024 May 20.
Article En | MEDLINE | ID: mdl-38727030

Medical implants are constantly facing the risk of bacterial infections, especially infections caused by multidrug resistant bacteria. To mitigate this problem, gold nanoparticles with alkyl bromide moieties (Au NPs-Br) on the surfaces were prepared. Xenon light irradiation triggered the plasmon effect of Au NPs-Br to induce free radical graft polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA), leading to the formation of poly(DMAEMA) brush-grafted Au NPs (Au NPs-g-PDM). The Au NPs-g-PDM nanocomposites were conjugated with phytic acid (PA) via electrostatic interaction and van der Waals interaction. The as-formed aggregates were deposited on the titanium (Ti) substrates to form the PA/Au NPs-g-PDM (PAP) hybrid coatings through surface adherence of PA and the gravitational effect. Synergistic bactericidal effects of contact-killing caused by the cationic PDM brushes, and local heating generated by the Au NPs under near-infrared irradiation, conferred strong antibacterial effects on the PAP-deposited Ti (Ti-PAP) substrates. The synergistic bactericidal effects reduced the threshold temperature required for the photothermal sterilization, which in turn minimized the secondary damage to the implant site. The Ti-PAP substrates exhibited 97.34% and 99.97% antibacterial and antiadhesive efficacy, respectively, against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), compared to the control under in vitro antimicrobial assays. Furthermore, the as-constructed Ti-PAP surface exhibited a 99.42% reduction in the inoculated S. aureus under in vivo assays. In addition, the PAP coatings exhibited good biocompatibility in the hemolysis and cytotoxicity assays as well as in the subcutaneous implantation of rats.


Anti-Bacterial Agents , Escherichia coli , Gold , Materials Testing , Metal Nanoparticles , Microbial Sensitivity Tests , Particle Size , Phytic Acid , Staphylococcus aureus , Gold/chemistry , Gold/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Metal Nanoparticles/chemistry , Phytic Acid/chemistry , Phytic Acid/pharmacology , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Animals , Surface Properties , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Cations/chemistry , Cations/pharmacology , Polymers/chemistry , Polymers/pharmacology , Titanium/chemistry , Titanium/pharmacology
10.
Pathog Dis ; 822024 Feb 07.
Article En | MEDLINE | ID: mdl-38730561

Antibiotic resistance (ATBR) is increasing every year as the overuse of antibiotics (ATBs) and the lack of newly emerging antimicrobial agents lead to an efficient pathogen escape from ATBs action. This trend is alarming and the World Health Organization warned in 2021 that ATBR could become the leading cause of death worldwide by 2050. The development of novel ATBs is not fast enough considering the situation, and alternative strategies are therefore urgently required. One such alternative may be the use of non-thermal plasma (NTP), a well-established antimicrobial agent actively used in a growing number of medical fields. Despite its efficiency, NTP alone is not always sufficient to completely eliminate pathogens. However, NTP combined with ATBs is more potent and evidence has been emerging over the last few years proving this is a robust and highly effective strategy to fight resistant pathogens. This minireview summarizes experimental research addressing the potential of the NTP-ATBs combination, particularly for inhibiting planktonic and biofilm growth and treating infections in mouse models caused by methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa. The published studies highlight this combination as a promising solution to emerging ATBR, and further research is therefore highly desirable.


Anti-Bacterial Agents , Biofilms , Plasma Gases , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Plasma Gases/pharmacology , Animals , Humans , Biofilms/drug effects , Pseudomonas aeruginosa/drug effects , Mice , Methicillin-Resistant Staphylococcus aureus/drug effects , Drug Resistance, Bacterial , Drug Resistance, Microbial , Pseudomonas Infections/microbiology , Pseudomonas Infections/drug therapy , Disease Models, Animal , Staphylococcal Infections/microbiology , Staphylococcal Infections/drug therapy
11.
PLoS One ; 19(5): e0301767, 2024.
Article En | MEDLINE | ID: mdl-38758936

The primary objective of this study was to isolate bacteria from diabetic foot ulcers and subsequently assess their antibiotic resistance capabilities. Seventy-five patients diagnosed with diabetic foot ulcers were investigated. A number of these patients (97.33%) had type 2 diabetes, with a significant proportion of them having been diagnosed for 1-5 years (29.33%). Notably, a substantial number of these individuals were on insulin usage (78.66%). Among the patients under examination, 49.33% reported having no use of tobacco products, alcohol, or betel leaf. The ulcers analyzed in this study were classified into grades 1-5 according to the Wagner scale. Wagner grade 2 diabetic foot ulcers had the highest number of culture-positive patients, at 33.33%. Pus samples collected from patients were cultured on selective media, and bacterial identity was confirmed by biochemical tests and polymerase chain reaction. A total of 141 isolates were isolated. Among the isolates, 82.97% gram-negative bacteria and 17.02% gram-positive bacteria were detected. Klebsiella pneumoniae was the most common isolate. Proteus spp., Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were also detected. Approximately 61.33% of the ulcers exhibited were polybacterial. In this study, it was observed that all bacterial isolates, except for Proteus spp., were primarily detected in patients classified under Wagner's grade 2. Moreover, antibiotic susceptibility was also tested on these 141 isolates. Among them, Escherichia coli showed the highest multidrug resistance, 81.81%. Most of the gram-negative bacteria were resistant to ampicillin. All of the gram-negative isolates exhibited high levels of susceptibility to piperacillin-tazobactam, and these levels were Klebsiella pneumoniae (97.56%), Pseudomonas aeruginosa (95.24%), Escherichia coli (81.82%), and Proteus spp. (80%). On the other hand, gram-positive Staphylococcus aureus mostly showed sensitivity towards vancomycin and norfloxacin (79.17%).


Anti-Bacterial Agents , Diabetic Foot , Microbial Sensitivity Tests , Humans , Diabetic Foot/microbiology , Diabetic Foot/drug therapy , Male , Female , Middle Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Bangladesh/epidemiology , Aged , Adult , Drug Resistance, Bacterial , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/isolation & purification , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Diabetes Mellitus, Type 2/microbiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Staphylococcus aureus/drug effects , Staphylococcus aureus/isolation & purification
12.
Chemosphere ; 358: 142223, 2024 Jun.
Article En | MEDLINE | ID: mdl-38704045

Antibiotic resistance (AR) is considered one of the greatest global threats in the current century, which can only be overcome if all interconnected areas of humans, animals and the environment are taken into account as part of the One Health concept proposed by the World Health Organization (WHO). Water and wastewater are among the most important environmental media of AR sources, where the phenomena are generally non-linear. Therefore, the aim of this study was to investigate the application of machine learning-based methods (MLMs) to solve AR-induced problems in water and wastewater. For this purpose, most relevant databases were searched in the period between 1987 and 2023 to systematically analyze and categorize the applications. Accordingly, the results showed that out of 12 applications, 11 (91.6%) were for shallow learning and 1 (8.3%) for deep learning. In shallow learning category, n = 6, 50% of the applications were regression and n = 4, 33.3% were classification, mainly using artificial neural networks, decision trees and Bayesian methods for the following objectives: Predicting the survival of antibiotic-resistant bacteria (ARB), determining the order of influencing parameters on AR-based scores, and identifying the major sources of antibiotic resistance genes (ARGs). In addition, only one study (8.3%) was found for clustering and no study for association. Surprisingly, deep learning had been used in only one study (8.3%) to predict ARGs sequences. Therefore, working on the knowledge gaps of AR, especially using clustering, association and deep learning methods, would be a promising option to analyze more aspects of the related problems. However, there is still a long way to go to consider and apply MLMs as unique approaches to study different aspects of AR in water and wastewater.


Machine Learning , Wastewater , Wastewater/microbiology , Drug Resistance, Microbial/genetics , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacteria/genetics , Bayes Theorem , Neural Networks, Computer , Drug Resistance, Bacterial/genetics
14.
ACS Nano ; 18(20): 13196-13213, 2024 May 21.
Article En | MEDLINE | ID: mdl-38717096

There is an increasingly growing demand to balance tissue repair guidance and opportunistic infection (OI) inhibition in clinical implant surgery. Herein, we developed a nanoadjuvant for all-stage tissue repair guidance and biofilm-responsive OI eradication via in situ incorporating Cobaltiprotoporphyrin (CoPP) into Prussian blue (PB) to prepare PB-CoPP nanozymes (PCZs). Released CoPP possesses a pro-efferocytosis effect for eliminating apoptotic and progressing necrotic cells in tissue trauma, thus preventing secondary inflammation. Once OIs occur, PCZs with switchable nanocatalytic capacity can achieve bidirectional pyroptosis regulation. Once reaching the acidic biofilm microenvironment, PCZs possess peroxidase (POD)-like activity that can generate reactive oxygen species (ROS) to eradicate bacterial biofilms, especially when synergized with the photothermal effect. Furthermore, generated ROS can promote macrophage pyroptosis to secrete inflammatory cytokines and antimicrobial proteins for biofilm eradication in vivo. After eradicating the biofilm, PCZs possess catalase (CAT)-like activity in a neutral environment, which can scavenge ROS and inhibit macrophage pyroptosis, thereby improving the inflammatory microenvironment. Briefly, PCZs as nanoadjuvants feature the capability of all-stage tissue repair guidance and biofilm-responsive OI inhibition that can be routinely performed in all implant surgeries, providing a wide range of application prospects and commercial translational value.


Biofilms , Pyroptosis , Biofilms/drug effects , Pyroptosis/drug effects , Animals , Mice , Reactive Oxygen Species/metabolism , Ferrocyanides/chemistry , Ferrocyanides/pharmacology , Prostheses and Implants , Macrophages/metabolism , Macrophages/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Wound Healing/drug effects , Humans , Efferocytosis
15.
Langmuir ; 40(20): 10589-10599, 2024 May 21.
Article En | MEDLINE | ID: mdl-38728854

Optically transparent glass with antifogging and antibacterial properties is in high demand for endoscopes, goggles, and medical display equipment. However, many of the previously reported coatings have limitations in terms of long-term antifogging and efficient antibacterial properties, environmental friendliness, and versatility. In this study, inspired by catfish and sphagnum moss, a novel photoelectronic synergy antifogging and antibacterial coating was prepared by cross-linking polyethylenimine-modified titanium dioxide (PEI-TiO2), polyvinylpyrrolidone (PVP), and poly(acrylic acid) (PAA). The as-prepared coating could remain fog-free under hot steam for more than 40 min. The experimental results indicate that the long-term antifogging properties are due to the water absorption and spreading characteristics. Moreover, the organic-inorganic hybrid of PEI and TiO2 was first applied to enhance the antibacterial performance. The Staphylococcus aureus and the Escherichia coli growth inhibition rates of the as-prepared coating reached 97 and 96% respectively. A photoelectronic synergy antifogging and antibacterial mechanism based on the positive electrical and photocatalytic properties of PEI-TiO2 was proposed. This investigation provides insight into designing multifunctional bioinspired surface materials to realize antifogging and antibacterial that can be applied to medicine and daily lives.


Anti-Bacterial Agents , Escherichia coli , Staphylococcus aureus , Titanium , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Titanium/chemistry , Titanium/pharmacology , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Polyethyleneimine/chemistry , Polyethyleneimine/pharmacology , Acrylic Resins/chemistry , Acrylic Resins/pharmacology , Microbial Sensitivity Tests , Povidone/chemistry , Surface Properties
16.
BMC Infect Dis ; 24(1): 501, 2024 May 17.
Article En | MEDLINE | ID: mdl-38760687

BACKGROUND: The study aims were to evaluate the species distribution and antimicrobial resistance profile of Gram-negative pathogens isolated from specimens of intra-abdominal infections (IAI), urinary tract infections (UTI), respiratory tract infections (RTI), and blood stream infections (BSI) in emergency departments (EDs) in China. METHODS: From 2016 to 2019, 656 isolates were collected from 18 hospitals across China. Minimum inhibitory concentrations were determined by CLSI broth microdilution and interpreted according to CLSI M100 (2021) guidelines. In addition, organ-specific weighted incidence antibiograms (OSWIAs) were constructed. RESULTS: Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the most common pathogens isolated from BSI, IAI and UTI, accounting for 80% of the Gram-negative clinical isolates, while Pseudomonas aeruginosa (P. aeruginosa) was mainly isolated from RTI. E. coli showed < 10% resistance rates to amikacin, colistin, ertapenem, imipenem, meropenem and piperacillin/tazobactam. K. pneumoniae exhibited low resistance rates only to colistin (6.4%) and amikacin (17.5%) with resistance rates of 25-29% to carbapenems. P. aeruginosa exhibited low resistance rates only to amikacin (13.4%), colistin (11.6%), and tobramycin (10.8%) with over 30% resistance to all traditional antipseudomonal antimicrobials including ceftazidime, cefepime, carbapenems and levofloxacin. OSWIAs were different at different infection sites. Among them, the susceptibility of RTI to conventional antibiotics was lower than for IAI, UTI or BSI. CONCLUSIONS: Gram-negative bacteria collected from Chinese EDs exhibited high resistance to commonly used antibiotics. Susceptibilities were organ specific for different infection sites, knowledge which will be useful for guiding empirical therapies in the clinic.


Anti-Bacterial Agents , Emergency Service, Hospital , Gram-Negative Bacteria , Gram-Negative Bacterial Infections , Microbial Sensitivity Tests , Humans , China/epidemiology , Anti-Bacterial Agents/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Emergency Service, Hospital/statistics & numerical data , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/epidemiology , Urinary Tract Infections/microbiology , Urinary Tract Infections/epidemiology , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/epidemiology , Intraabdominal Infections/microbiology , Intraabdominal Infections/epidemiology , Drug Resistance, Bacterial , Female , Male
17.
BMC Microbiol ; 24(1): 172, 2024 May 18.
Article En | MEDLINE | ID: mdl-38760693

BACKGROUND: We evaluated whether the sputum bacterial microbiome differs between nontuberculous mycobacteria pulmonary disease (NTM-PD) patients with stable disease not requiring antibiotic treatment and those requiring antibiotics. METHODS: We collected sputum samples from 21 clinically stable NTM-PD patients (stable group) and 14 NTM-PD patients needing antibiotic treatment (treatment group). We also obtained 13 follow-up samples from the stable group. We analyzed the 48 samples using 16S rRNA gene sequencing (V3-V4 region) and compared the groups. RESULTS: In the linear discriminant analysis effect size (LEfSe) analysis, the species Porphyromonas pasteri, Haemophilus parahaemolyticus, Prevotella nanceiensis, and Gemella haemolysans were significantly more prevalent in the sputum of the stable group compared to the treatment group. No taxa showed significant differences in alpha-/beta-diversity or LEfSe between the 21 baseline and 13 follow-up sputum samples in the stable group. In the stable group, the genus Bergeyella and species Prevotella oris were less common in patients who achieved spontaneous culture conversion (n = 9) compared to those with persistent NTM positivity (n = 12) (effect size 3.04, p = 0.039 for Bergeyella; effect size 3.64, p = 0.033 for P. oris). In the treatment group, H. parainfluenzae was more common in patients with treatment success (n = 7) than in treatment-refractory patients (n = 7) (effect size 4.74, p = 0.013). CONCLUSIONS: Our study identified distinct bacterial taxa in the sputum of NTM-PD patients based on disease status. These results suggest the presence of a microbial environment that helps maintain disease stability.


Microbiota , Mycobacterium Infections, Nontuberculous , RNA, Ribosomal, 16S , Sputum , Humans , Sputum/microbiology , Male , Female , Microbiota/genetics , Microbiota/drug effects , Aged , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium Infections, Nontuberculous/drug therapy , RNA, Ribosomal, 16S/genetics , Middle Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Nontuberculous Mycobacteria/isolation & purification , Nontuberculous Mycobacteria/genetics , Nontuberculous Mycobacteria/classification , Nontuberculous Mycobacteria/drug effects , DNA, Bacterial/genetics , Lung Diseases/microbiology , Lung Diseases/drug therapy
18.
Clin Oral Investig ; 28(6): 323, 2024 May 18.
Article En | MEDLINE | ID: mdl-38761310

OBJECTIVES: White spot lesions are the most common iatrogenic effect observed during orthodontic treatment. This study aimed to compare the surface characteristics and antibacterial action of uncoated and coated orthodontic brackets. MATERIALS AND METHODS: Sixty commercially available stainless steel brackets were coated with TiO2 nanotubes and methacryloyloxyethylphosphorylcholine. The sample was divided into Group 1: uncoated orthodontic brackets, Group 2: Stainless steel brackets with TiO2 nanotubes coating, Group 3: Stainless steel brackets with methacryloyloxyethylphosphorylcholine coating, and Group 4: Stainless steel brackets with TiO2 nanotubes combined with methacryloyloxyethylphosphorylcholine coating. Surface characterization was assessed using atomic force microscopy and scanning electron microscopy. Streptococcus mutans was selected to test the antibacterial ability of the orthodontic brackets, total bacterial adhesion and bacterial viability were assessed. The brackets were subjected to scanning electron microscopy to detect the presence of biofilm. RESULTS: The surface roughness was the greatest in Group 1 and least in Group 2 followed by Group 4 and Group 3 coated brackets. The optical density values were highest in Group 1 and lowest in Group 4. Comparison of colony counts revealed high counts in Group 1 and low counts in Group 4. A positive correlation between surface roughness and colony counts was obtained, however, was not statistically significant. CONCLUSIONS: The coated orthodontic brackets exhibited less surface roughness than the uncoated orthodontic brackets. Group 4 coated orthodontic brackets showed the best antibacterial properties. CLINICAL RELEVANCE: Coated orthodontic brackets prevent adhesion of streptococcus mutans and reduces plaque accumulation around the brackets thereby preventing formation of white spot lesions during orthodontic treatment.


Anti-Bacterial Agents , Bacterial Adhesion , Microscopy, Electron, Scanning , Nanotubes , Orthodontic Brackets , Phosphorylcholine , Streptococcus mutans , Surface Properties , Titanium , Titanium/chemistry , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/pharmacology , Phosphorylcholine/chemistry , Streptococcus mutans/drug effects , Anti-Bacterial Agents/pharmacology , Nanotubes/chemistry , Bacterial Adhesion/drug effects , Microscopy, Atomic Force , Materials Testing , Stainless Steel/chemistry , Methacrylates/pharmacology , Methacrylates/chemistry , Biofilms/drug effects , Coated Materials, Biocompatible/pharmacology , Coated Materials, Biocompatible/chemistry
19.
BMC Microbiol ; 24(1): 173, 2024 May 18.
Article En | MEDLINE | ID: mdl-38762474

BACKGROUND: The persistent surge in antimicrobial resistance represents a global disaster. The initial attachment and maturation of microbial biofilms are intimately related to antimicrobial resistance, which in turn exacerbates the challenge of eradicating bacterial infections. Consequently, there is a pressing need for novel therapies to be employed either independently or as adjuvants to diminish bacterial virulence and pathogenicity. In this context, we propose a novel approach focusing on vitamin D and vitamin K1 as potential antibiofilm agents that target Gram-negative bacteria which are hazardous to human health. RESULTS: Out of 130 Gram-negative bacterial isolates, 117 were confirmed to be A. baumannii (21 isolates, 17.9%), K. pneumoniae (40 isolates, 34.2%) and P. aeruginosa (56 isolates, 47.9%). The majority of the isolates were obtained from blood and wound specimens (27.4% each). Most of the isolates exhibited high resistance rates to ß-lactams (60.7-100%), ciprofloxacin (62.5-100%), amikacin (53.6-76.2%) and gentamicin (65-71.4%). Approximately 93.2% of the isolates were biofilm producers, with 6.8% categorized as weak, 42.7% as moderate, and 50.4% as strong biofilm producers. The minimum inhibitory concentrations (MICs) of vitamin D and vitamin K1 were 625-1250 µg mL-1 and 2500-5000 µg mL-1, respectively, against A. baumannii (A5, A20 and A21), K. pneumoniae (K25, K27 and K28), and P. aeruginosa (P8, P16, P24 and P27) clinical isolates and standard strains A. baumannii (ATCC 19606 and ATCC 17978), K. pneumoniae (ATCC 51503) and P. aeruginosa PAO1 and PAO14. Both vitamins significantly decreased bacterial attachment and significantly eradicated mature biofilms developed by the selected standard and clinical Gram-negative isolates. The anti-biofilm effects of both supplements were confirmed by a notable decrease in the relative expression of the biofilm-encoding genes cusD, bssS and pelA in A. baumannii A5, K. pneumoniae K28 and P. aeruginosa P16, respectively. CONCLUSION: This study highlights the anti-biofilm activity of vitamins D and K1 against the tested Gram-negative strains, which emphasizes the potential of these vitamins for use as adjuvant therapies to increase the efficacy of treatment for infections caused by multidrug-resistant (MDR) strains and biofilm-forming phenotypes. However, further validation through in vivo studies is needed to confirm these promising results.


Anti-Bacterial Agents , Biofilms , Gram-Negative Bacteria , Microbial Sensitivity Tests , Vitamin D , Vitamin K 1 , Biofilms/drug effects , Biofilms/growth & development , Humans , Vitamin K 1/pharmacology , Anti-Bacterial Agents/pharmacology , Vitamin D/pharmacology , Gram-Negative Bacteria/drug effects , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/physiology , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/drug therapy , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/physiology , Acinetobacter baumannii/isolation & purification , Drug Resistance, Multiple, Bacterial/drug effects
20.
BMC Infect Dis ; 24(1): 502, 2024 May 18.
Article En | MEDLINE | ID: mdl-38762526

BACKGROUND: Urinary tract infections (UTIs) are one of the most common health problems worldwide and mainly affect women. This study aimed to evaluate the prevalence of UTIs in pregnant women and determine the antimicrobial resistance patterns of bacterial pathogens isolated from pregnant and nonpregnant women in Riyadh, Saudi Arabia. METHODS: This retrospective cohort study was conducted at an academic medical center in Riyadh, Saudi Arabia, from January to June 2022. The study included all urine cultures performed for adult women during the study period. We excluded urine culture performed for women on antibiotics prescribed for any infection, children, and men. Using the SPSS (version 27) package, descriptive statistics and chi-square tests were used to analyze the data, and p < 0.05 was considered to indicate statistical significance. RESULTS: A total of 2,418 urine cultures performed during the study period were included (985 and 1,433 for pregnant and nonpregnant women, respectively). The overall prevalence of UTIs in pregnant women was 5% (95% CI 3.6-6.4); 10 (1%) women were symptomatic, and 40 (4%) women were asymptomatic. Of the entire cohort, 244 (10.1%) women were diagnosed with UTIs based on bacterial cultures. The predominant bacteria in both pregnant and nonpregnant women were Escherichia coli (134, 54.9%), followed by Klebsiella pneumoniae (48, 19.6%). The antibiotic susceptibility criteria for Escherichia coli and Klebsiella pneumoniae were as follows: nitrofurantoin (94% and 18.8%, respectively), amoxicillin-clavulanic acid (82.8% and 70.8%, respectively), ciprofloxacin (65.7% and 83.3%, respectively), trimethoprim-sulfamethoxazole (65.7% and 79.2%, respectively) and cephalothin (47% and 68.8%, respectively). CONCLUSION: Compared to the findings of other similar studies, the prevalence of UTIs was lower in pregnant women. This may be because the patient population was composed of healthy and educated women who received prenatal education and underwent prenatal assessment as per institutional guidelines. Nitrofurantoin and amoxicillin-clavulanic acid are recommended for use as an empirical therapy for UTIs in pregnant and nonpregnant women because bacteria have the least amount of resistance to these drugs.


Anti-Bacterial Agents , Drug Resistance, Bacterial , Urinary Tract Infections , Humans , Female , Urinary Tract Infections/microbiology , Urinary Tract Infections/epidemiology , Urinary Tract Infections/drug therapy , Saudi Arabia/epidemiology , Pregnancy , Retrospective Studies , Adult , Prevalence , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Young Adult , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/microbiology , Pregnancy Complications, Infectious/drug therapy , Microbial Sensitivity Tests , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Bacteria/drug effects , Bacteria/isolation & purification , Bacteria/classification , Middle Aged
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